Gene Expression Profiling On Insulin Resistance And Obes

胰岛素抵抗和肥胖的基因表达谱

• 批准号: 7337553
• 负责人: Clifton Bogardus
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7337553
• 关键词: Gene; Expression; Profiling; Insulin; Resistance

We performed global gene expression profiling to complement the ongoing positional cloning effort to identify susceptibility genes for diabetes and its predictors, insulin resistance and obesity. To this end, we have examined gene expression profiles in tissue samples from non-diabetic full-blooded Pima Indians using differntial-display PCR and human oligonucleotide microarrays containing 6800 genes and 35000 expressed sequence tags (ESTs). To identify possible determinants of insulin resistance, independent of the effects of obesity, differentially expressed genes were identified in skeletal muscle samples from a group of equally obese Pimas, matched for obesity, age and sex. To identify possible determinants of obesity, we identified differentially expressed genes in isloated, subcutaneous, abdominal adipocytes from a group of severly obese and lean Pimas matched for age and sex. To identify genes that were potentially secondarily differentially expressed, (e.g. as a result of hyperinsulinemia), we also determined leveles of gene expression in pre-adipocytes grown from these same adipose tissue samples. We have also now collected ~250 skeletal muscle tissue samples and ~150 adipose tissue samples from non-diabetic Pima Indians and are hybridizing to Affymetrix 1.2 million exon arrays to determine the gene expresion profile in these tissues associated with later development of type 2 diabetes.

我们进行了全球基因表达分析，以补充持续的位置克隆努力，以鉴定糖尿病及其预测因子，胰岛素抵抗和肥胖的易感基因。为此，我们使用了不同的display pcr和人类寡核苷酸微阵列，研究了非糖尿病全血PIMA印第安人的组织样品中的基因表达谱，其中包含6800个基因和35000个表达序列标签（ESTS）。 为了鉴定胰岛素抵抗的可能决定因素，与肥胖的作用无关，在一组同样肥胖的皮马的骨骼肌样本中鉴定出差异表达的基因，与肥胖，年龄和性别相匹配。为了鉴定肥胖症的可能决定因素，我们从一组与年龄和性别相匹配的一组肥胖和瘦肉皮马的等层，皮下，腹部脂肪细胞中鉴定出差异表达的基因。为了鉴定潜在地差异表达的基因（例如，由于高胰岛素血症），我们 还确定了从这些相同脂肪组织样品生长的前脂肪细胞中基因表达的水平。 我们现在还收集了〜250个骨骼肌组织样品和〜150个脂肪组织样品 来自非糖尿病PIMA印第安人，并与Affymetrix杂交120万个外显子阵列，以确定这些组织中与随后的2型糖尿病发育有关的这些组织中的基因排放谱。